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Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Meaningful Equity, Diversity, and Inclusion (EDI) efforts may be stymied by concerns about whether proposed initiatives are performative or tokenistic. The purpose of this project was to analyze discussions by the Research in Medical Education (RIME) Program Planning committee about how best to recognize and support underrepresented in medicine (URiM) researchers in medical education to generate lessons learned that might inform local, national, and international actions to implement meaningful EDI initiatives. Ten RIME Program Planning Committee members and administrative staff participated in a focus group held virtually in August 2021. Focus group questions elicited opinions about “if and how” to establish a URiM research award. The focus group was recorded, transcribed, and thematically analyzed. Recognition of privilege, including who has it and who doesn’t, underpinned the focus group discussion, which revolved around 2 themes: (1) tensions between optics and semantics, and (2) potential unintended consequences of trying to level the medical education playing field. The overarching storyline threaded throughout the focus group discussion was intentionality. Focus group participants sought to avoid performativity by creating an award that would be meaningful to recipients and to career gatekeepers such as department chairs and promotion and tenure committees. Ultimately, participants decided to create an award that focused on exemplary Equity, Diversity, and Inclusion (EDI) scholarship, which was eventually named the “RIME URiM Research Award.” Difficult but productive conversations about EDI initiatives are necessary to advance underrepresented in medicine (URiM) scholarship. This transparent commentary may trigger further critical conversations.

The gastric conduit is commonly created after esophagectomy to restore intestinal continuity. In this review, we discuss several complications that can arise and can be managed by a gastroenterologist. We highlight endoscopic management of anastomotic leaks and strictures. We also describe the work up and management of reflux disease, delayed gastric conduit emptying, and dumping syndrome, all of which can complicate short- and long-term outcomes in patients receiving a gastric conduit.

Abstract Background The optimal duration of antibiotic therapy after debridement and implant retention (DAIR) for periprosthetic joint infections (PJIs) is debated. Furthermore, the best antibiotic regimens for staphylococcal PJI are also unclear. In this study, we evaluated the impact of antibiotic therapy duration on the risk of failure. We assessed the utility of rifampin-based regimens for staphylococcal PJI managed with DAIR. Methods We performed a retrospective cohort study of patients 18 years and older diagnosed with hip and knee PJI who underwent DAIR between January 1, 2008 and 31 December 31, 2018 at Mayo Clinic, USA. The outcome was failure of DAIR. For statistical analysis, joint-stratified Cox regression models adjusted for age, sinus tract, symptom duration, and primary/revision arthroplasty were performed. Results We examined 247 cases of PJI with a median follow-up of 4.4 years (interquartile range [IQR], 2.3–7) after DAIR. The estimated 5-year cumulative incidence of failure was 28.1% (n = 65). There was no association between the duration of intravenous (IV) antibiotics (median 42 days; IQR, 38–42) and treatment failure (P = .119). A shorter duration of subsequent oral antibiotic therapy was associated with a higher risk of failure (P = .005; eg, 90-day vs 1-year duration; hazard ratio [HR], 3.50; 95% confidence interval [CI], 1.48–8.25). For staphylococcal knee PJI, both the use and longer duration of a rifampin-based regimen were associated with a lower risk of failure (both P = .025). There was no significant association between fluoroquinolone (FQ) use and failure (HR, 0.62; 95% CI, .31–1.24; P = .172). Conclusions The duration of initial IV antibiotic therapy did not correlate with treatment failure in this cohort of patients. Rifampin use is recommended for staphylococcal knee PJI. There was no apparent benefit of FQ use in staphylococcal PJI.

e19553 Background: The combination of tafa + LEN has accelerated approval in the United States (2020) and conditional approval in Canada and Europe (2021) for R/R DLBCL in ASCT-ineligible adult pts. A tolerable safety profile for R-CHOP + tafa ± LEN in pts with newly diagnosed DLBCL in the Phase Ib First-MIND study (NCT04134936) was previously reported, with numerically superior efficacy for R-CHOP + tafa + LEN (ASH 2021; #3556). We report PK, PD, and immunogenicity of R-CHOP + tafa ± LEN in this first line setting. Methods: Eligible pts ≥18 years with treatment-naïve DLBCL, IPI 2–5, and ECOG PS 0–2 were randomized 1:1 to either six 21-day (D) cycles (C) of R-CHOP (R-CHO, D1; P, D1–5) + tafa (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafa + LEN (25 mg orally, D1–10) (Arm B). Secondary endpoints included tafa serum conc and number and percentage of pts developing anti-tafa Abs. Exploratory endpoints included natural killer (NK) cell, T-cell, and B-cell count in peripheral blood. Results: Data cut-off: 13 March 2021 for safety analysis, incl. ≥1 month follow-up after EoT visit for all pts; 15 September 2021 for efficacy. Tafa serum conc reached steady state by C3 (geometric mean trough conc: Arm A, 186.40–216.55 µg/mL; Arm B, 171.77–201.54 µg/mL) and steadily declined after treatment completion. Anti-tafa Abs were detected in 1/65 (1.5%) pts. This pt showed pre-existing tafa Abs at baseline, which decreased during treatment. Median NK cell count decreased from baseline at C1D8 but was at baseline or higher levels by EoT visit (Arm A) and C1D15 (Arm B; Table). T-cell count decreased from baseline at C1D8 in both arms but was at baseline level or higher by C1D15 (Arm A) and EoT visit (Arm B). Median B-cell count decreased from baseline to 0 cells/μL (Arm A, C1D15; Arm B, C1D8); at 6-month follow-up after EoT visit, B-cell count had recovered to measurable levels in ̃50% of pts. Conclusions: Tafa serum conc reached and maintained a therapeutic dose level in this first-line regimen and declined in line with known tafa half-life (̃16 days) after treatment completion; tafa levels were comparable between the two treatment arms. No pt developed treatment-induced or treatment-boosted anti-tafa Abs. Median NK-cell, T-cell, and B-cell counts were comparable between treatment arms in all cycles. Clinical trial information: NCT04134936. [Table: see text]

Abstract Introduction Introduction: Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) is characterized by a lack of muscle atonia during REM sleep with dream enactment. RBD is regarded as a prodromal synucleinopathy as a high proportion of patients eventually phenoconvert to Parkinson’s Disease and related synucleinopathies, suggesting RBD may be an early non-motor symptom of disease. Accordingly, patients with RBD are ideally situated to test potential therapeutic interventions to prevent phenoconversion to synucleinopathy. However, RBD itself, and associated patient registries, are rare. The North American Prodromal Synucleinopathy Consortium (NAPS) establishes a multisite registry of RBD patients with standardized neurological, neuropsychiatric, and neuropsychological assessments and biomarker collection. The present work reports baseline characteristics of this RBD patient database at its current state. Methods Methods: Participants >18 years of age with overnight polysomnogram-confirmed RBD by ICSD-3 criteria who did not meet criteria for the diagnosis of PD, dementia, MSA, or narcolepsy were enrolled from 10 sites across North America (8/2018 to 4/2021). Data collection included family and personal history of RBD and related symptoms, as well as standardized assessments related to cognitive, motor, sensory and autonomic function. Additionally, all subjects have contributed blood, and a subset of subjects have contributed cerebrospinal fluid samples to the National Centralized Repository for Alzheimer's Disease and Related Dementias for future analysis. Results Results: A total of n=251 participants were enrolled. Outcomes are reported based on sex (n=202 male, n=49 female). Data were further examined based on participants’ history of antidepressant use (n=142 with, n=103 without) and based on participants’ extent of synucleinopathy burden (n=70 defined as isolated RBD, n=181 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Any observed sex differences among the data did not persist after correction for antidepressant use. Conclusion Conclusions: This prospective, cross-sectional data on history, demographic, cognitive, motor, sensory, and autonomic function in n=251 participants with RBD highlight the lack of sex differences and the high preponderance of concomitant neurological abnormalities with RBD, and provide a valuable registry for future longitudinal studies and neuroprotective clinical trials. Support (If Any) NIH NIA R34 AG056639 (YJ, BB)

Purpose: To identify risk factors for the development of new-onset, postoperative diplopia following orbital decompression surgery based on patient demographics, clinical exam characteristics, radiographic parameters, and surgical techniques. Methods: We conducted a multi-center retrospective chart review of patients who underwent orbital decompression for thyroid eye disease (TED). Patient demographics, including age, gender, smoking history, preoperative exophthalmometry, clinical activity score (CAS), use of peribulbar and/or systemic steroids, and type of orbital decompression were reviewed. Postoperative diplopia was determined at a minimum of 3 months postoperatively and before any further surgeries. Cross-sectional area ratios of each extraocular muscle to orbit and total fat to orbit were calculated from coronal imaging in a standard fashion. All measurements were carried out using PACS imaging software. Multivariable logistic regression modeling was performed using Stata 14.2 (StataCorp, College Station, TX). Results: A total of 331 patients without preoperative diplopia were identified. At 3 months postoperatively, 249 patients had no diplopia whereas 82 patients developed diplopia. The average postoperative follow-up was 22 months (range 3–156) months. Significant preoperative clinical risk factors for postoperative diplopia included older age at surgery, proptosis, use of peribulbar or systemic steroids, elevated clinical activity score, and presence of preoperative compressive optic neuropathy. Imaging findings of enlarged cross-sectional areas of each rectus muscle to the overall orbital area also conferred a significant risk of postoperative diplopia. Regarding surgical factors, postoperative diplopia was more common among those undergoing medial wall decompression, bilateral orbital surgery, and balanced decompression, whereas endoscopic medial wall decompression was found to be relatively protective. Conclusions: This study identifies risk factors associated with the development of diplopia following orbital decompression using multivariable data. This study demonstrates that several characteristics including age, clinical activity score, the cross-sectional muscle to orbit ratios, in addition to the type of orbital decompression surgery, are predictive factors for the development of new-onset postoperative diplopia.

Abstract Background Corynebacterium periprosthetic joint infection (PJI) is a poorly described infectious syndrome. Prior studies included cases of polymicrobial infections. This series describes the clinical characteristics, management, and outcomes of monomicrobial Corynebacterium PJI. Methods We queried the Mayo Clinic Total Joint Registry for cases of monomicrobial Corynebacterium knee and hip PJI in adults (age ≥18 years) between 2010 and 2019. Results A total of 20 (1%) out of 2067 PJI cases met our inclusion criteria. Most were males (55%), and the median age was 64 years. Seventy percent had chronic symptoms (>4 weeks). PJI was delayed to late (>3 months postimplantation) in 90%. Three species were identified: C. striatum (70%), C. jeikeium (20%), and C. amycolatum (10%). All tested isolates were susceptible to vancomycin (100%) and linezolid (100%), and most had a minimum inhibitory concentration ≤0.06 mcg/mL to daptomycin (75%). Other agents were less reliable, with high resistance to oral agents commonly used for suppression. Nineteen patients were treated: 37% debridement and implant retention (DAIR), 47% 2-stage exchange, and 16% resection without reimplantation. Of these, failure occurred in 29%, 11%, and 0%, respectively. Conclusions Corynebacterium PJIs pose a therapeutic challenge due to limited antimicrobial armamentarium and undefined optimal surgical intervention. Vancomycin and linezolid remain the most reliable agents for treatment. DAIR may be attempted for acute PJI, but verification of durable chronic suppression options will be critical for this approach.